Low efficacy of thalidomide in improving response after induction in multiple myeloma patients who are candidates for high-dose therapy.

Giving the impact of complete response (CR) on outcome of multiple myeloma patients addressed to high-dose melphalan, we explored the role of a pre-transplant intensification with 3 months thalidome plus dexamethasone therapy (Thal-Dex), after pulse-VAD induction. Seventy-four multiple myeloma patients (MM pts) uniformly treated, were retrospectively studied. The response rate after pulse-VAD were: CR 6%, VGPR 40%, PR 23%, MR 23%, and progression 8%. The response rate after Thal-Dex were similar: CR 11%, VGPR 39%, PR 17%, MR 9%, and progression 24%. Giving no advantage in terms of response rate with an additive toxicity, Thal-Dex does not seem useful for intensification before transplant.

Familial hemiplegic migraine versus migraine with prolonged aura: an uncertain diagnosis in a family report.

Four of five members of a family complained of repeated attacks of hemiplegic migraine, migraine with aura of different types, or migraine without aura. The hemiplegia always outlasted the headache and was often accompanied by altered consciousness, aphasia, and, in one patient, coma; in this latter patient, the ictal EEG, recorded during two attacks, showed delta activity in the hemisphere contralateral to the hemiplegia. At least 2 months after their latest attacks, three patients showed dyscalculia, attentional disturbances, and impaired long-term verbal memory on neuropsychologic assessment. There were no cognitive disturbances in the unaffected relative. The severity of cognitive impairment appears to be correlated with migraine history. We attempt to classify these cases according to the criteria of the International Headache Society.

Influence of different anaesthetics on extracellular aminoacids in rat brain.

We used different anaesthetic procedures to study the possible effects of anaesthesia on extracellular aminoacid concentration in rat brain. Glutamate, aspartate and glycine concentrations were determined by HPLC in samples collected from the right fronto-parietal region of the rat brain cortex by transcerebral microdialysis before and up to 2 h following anaesthesia induction. Anaesthesia induced by ketamine, alone or in association with xylazine, caused a significant decrease in the levels of glutamate, aspartate and glycine, compared to before anaesthesia values (range: 27-72% according to the time of sampling and to the anaesthetic used). Inhalation anaesthesia with halothane (3%) in N2O/O2 mixture produced no significant effects on aminoacid levels. Equitensine (pentobarbital in association with chloral hydrate and ethanol) and pentobarbital also had no significant effect on glutamate, aspartate and glycine levels during anaesthesia. This demonstrates that some anaesthetics alter excitatory aminoacid release and suggests that Equitensine may represent an easy and reliable method to induce a long lasting anaesthesia associated without changes in excitatory aminoacid extracellular concentration.

A cooperative study on ProMACE-CytaBOM in aggressive non-Hodgkin's lymphomas.

Chemotherapy using cyclophosphamide, doxorubicin, etoposide, cytarabine, bleomycin, vincristine, methotrexate with leucovorin, and prednisone (ProMACE-CytaBOM) for patients with intermediate or high grade non-Hodgkin lymphomas (G, H and K according to the Working Formulation), was tested by the Gruppo Cooperativo Lombardo to confirm the activity of the regimen and to test the feasibility and safety of administering third-generation drug regimen in a cooperative group setting. Among 64 previously untreated patients, aged between 20 and 71 years, 7 had stage IB-IIB, 12 had stage IIIA-B, 45 (67%) had stage IVA-B. There were 44 complete remissions (CRs) (69%) and 14 partial remissions (22%); the difference between patients in stage I-II-III (84% complete remissions) and those in stage IV (62% complete remissions) was statistically significant. The median length of follow up was 20 months (range 1-60 months), with 56% of patients alive at 60 months and 53% of CRs patients free of disease at 60 months. Patients in stage I-II-III have the best survival and disease free survival compared to stage IV, 87% versus 42% and 72% versus 32% respectively (both with high statistical significance). Grade 3-4 (WHO) haematological toxicity was observed in 39% of patients, with 3 septic deaths. Two more patients died with chemotherapy related toxicity (1 stroke and 1 acute renal insufficiency). Administration of ProMACE-CytaBOM is a feasible and safe regimen although it presents moderate toxicity. ProMACE-CytaBOM may represent improved treatment for aggressive lymphomas, in terms of duration of response and survival, but a longer follow up is needed.

Aminoacid recovery via microdialysis and photoinduced focal cerebral ischemia in brain cortex of rats.

A photochemical method using the Rose Bengal dye as thrombogenic agent was employed to induce focal cerebral ischemia in frontoparietal cortex of rats. A transcerebral microdialysis probe was used to collect samples from ischemic cortical area. An increase in glutamate (6-fold) and in taurine (4-fold) within the first hour occurred. Neuropathological investigations demonstrate a reproducible damaged area surrounded by a thin peripheral area showing neuronal apoptotic phenomena. The method represents a reproducible model of focal cerebral ischemia with neuropathological aspects superimposable to those characteristic of thrombogenic stroke in man. This method could also be relevant in the study of neurotransmitters during the evolution of ischemia. Furthermore, the presence of apoptotic phenomena in the perilesional halo confirms an ischemic penumbra suggesting the significance of preclinical pharmacological trials.

Reference values of neuroactive amino acids in the cerebrospinal fluid by high-performance liquid chromatography with electrochemical and fluorescence detection.

Sampling and HPLC analysis procedures for CSF amino acid determinations were evaluated. In order to increase sensitivity, a precolumn derivatization of amino acids by o-phthalaldehyde-mercaptoethanol reagent was used. By using fluorimetric and electrochemical detection in series, positive peak identification can be obtained in a single chromatographic run. It is recommended to analyze freshly collected CSF. Amino acids are stable for short periods over a wide range of temperature, but storage at -80 degrees C is recommended. The CSF samples for the calculation of the reference values were taken from 40 healthy subjects, hospitalized for lumbar disk herniation, placed on the same diet and kept drug-free for at least 1 week. The mean values (mumol/l) and the ranges (in parentheses) were: 0.27 (0.09-0.63), 0.62 (0.18-1.15), 5.32 (3.05-11.50), 6.16 (2.90-13.30), 0.16 (0.03-0.22) for aspartic acid, glutamic acid, glycine, taurine and gamma-aminobutyric acid respectively.

Nitrite/nitrate balance during photoinduced cerebral ischemia in the rat determined by high-performance liquid chromatography with UV and electrochemical detection.

A specific and simple method for the direct simultaneous detection of extracellular nitrite (NO2-) and nitrate (NO3-) has been developed, using high-performance liquid chromatography separation with UV and electrochemical detection in series. These stable endproducts of nitric oxide (NO.) were determined in dialysis perfusate obtained through in vivo brain microdialysis during and after experimental photoinduced cerebral ischemia in rats. The chromatographic conditions were optimized with a reversed-phase column (250 x 46 mm) using 10 mM n-octylamine pH 6.0 as a mobile phase. Absorbance was measured at 220 nm for NO3- detection; electrochemical detection was performed at +0.7 V for NO2- evaluation. This assay system holds the advantages of in vivo consecutive measurements, high precision, good reproducibility, technical simplicity, fast response (about 7 min), and wide availability.

Bone marrow biopsy for the staging of non-Hodgkin's lymphoma: bilateral or unilateral trephine biopsy?

AIM: The occurrence of unilateral involvement in bilateral bone marrow trephine biopsies in non-Hodgkin's lymphomas (NHL) at disease onset (10-20% of cases) has been reported since the early 70s. Therefore, although these studies were based on small series, the use of bilateral bone marrow biopsies has become the rule. However, the clinical value of this procedure has never been clearly established. The aim of the present study was to ascertain the true value of bilateral bone marrow biopsy in the staging of NHL. STUDY DESIGN: We examined 368 cases of NHL (A-H according to the Working Formulation) (WF), without leukemic involvement of the peripheral blood, in order to evaluate: 1) the incidence of unilateral bone marrow involvement; 2) the percentage of patients who, as a result of unilateral bone marrow involvement, changed from stages I-II to stage IV; 3) assessment of response to therapy for patients with both bilateral or unilateral bone marrow involvement. RESULTS: In the A-C NHL groups of WF there was a unilateral bone marrow involvement of 8.8%. Overall, bone marrow involvement induced a change from clinical stages I-II to stage IV in 5.6% of cases, a figure which would correspond to a false negative rate of 2.8%, if unilateral bone marrow biopsy was performed. In the D-F and G, H groups of WF, unilateral involvement was 10.1% and 8.5% respectively; the change in stage from I-II to IV by unilateral bone marrow involvement respectively amounted to 1.4% and 2.8%, which correspond to respective false negative rates of 0.7% and 1.4%. CONCLUSIONS: On the basis of these results and of the present therapeutic strategies, we propose: bilateral bone marrow biopsy for clinical stages I-II of all NHL; no bone marrow biopsy at disease onset for clinical stages III and IV of A to H histologic subtypes of the WF; unilateral bone marrow biopsy (A-C subtypes of the WF) or bilateral (D-H of the WF), after the regression of extramedullary localizations.

[Primary lymphoma of the kidney. Description of a case and brief review of the literature]. / Il linfoma primitivo del rene. Descrizione di un caso e breve revisione della letteratura.

Stage IV disseminated non-Hodgkin lymphomas show kidney involvement with frequency; on the contrary, primary kidney lymphoma, as the sole presenting feature, is a very rare disease. Non-Hodgkin histological pattern, atypical symptoms, marked discrepancy between parenchymal involvement and impairment of renal function are the main features of this tumor. A case-report of a primary kidney non-Hodgkin lymphoma will be described; a short review of literature on this subject will be discussed.

[Topical treatment of thrombophlebitis with feprazone and benzydamine. Controlled clinical study]. / Trattamento topico delle tromboflebiti con feprazone e benzidamina. Studio clinico controllato

Topical anti-inflammatory management of superficial and deep phlebopathy with feprazone and benzidamine was compared in a double-blind test. Both drugs were active and well tolerated. Significantly less time was needed to obtain a cure with feprazone.

[Hypercalcemic syndrome in malignant lymphomas. Review of the literature and clinical contribution]. / La sindrome ipercalcemica nei linfomi maligni. Revisione della letteratura e contributo clinico.

The appearance of hypercalcemic syndrome during the course of lymphoma is not only an unusual event, but it puts a very difficult diagnostic and therapeutic question too. There are three aetiologic moments: the diffuse osseus metastases, the paraneoplastic syndrome and concomitant primitive hyperparathyroidism. The pathogenesis of these questions has lately stimulated a new kind of research, even if there are still a lot of unknown points. The Authors suggest, as their own contribution, the revision of the literature on this subject and they also suggest an acute hypercalcemic syndrome case brought about a primitive hyperparathyroidism in a patient suffering from Hodgkin's lymphoma.

[Malignant histiocytosis. Clinical contribution and review of the subject]. / L'istiocitosi maligna. Contributo clinico e revisione dell'argomento.

Malignant histiocytosis (MH) is a rare and severe disease caused by malignant histiocyte degeneration in the sinuses of the reticuloendothelial system. The clinical picture presents fever, wasting, enlargement of the liver and spleen and lymphoadenopathy. Diagnosis is based on histological criteria and it may prove very difficult to differentiate between MH and malignant lymphomas, acute monocytic leukemia and the histiocytoses considered benign. The main features of the disease are described with comments on two personally experienced clinical cases. Emphasis is placed on the leukaemic aspect, the involvement of the CNS, the association, in one case, with sarcoidosis and the poor prognosis.

[Splenic lymphoma with villous lymphocytes. A clinical case]. / Linfoma splenico con linfociti villosi. Caso clinico.

Splenic lymphoma with circulating villous lymphocytes is a rare B-lymphoproliferative disorder of the elderly which has been only recently defined. Clinical features are spleen enlargement of various degree without lymphadenopathy and an indolent course, with a long survival, in most cases. Absolute lymphocytosis is present; atypical circulating lymphocytes show a medium or large size, a small prominent nucleolus and a few short and thin cytoplasmic protrusions and projections (villi), which are distributed at one or both poles of cell surface. Reaction for tartrate-resistant acid phosphatase is almost always negative. Immunological markers are as follows: CD 19+, CD 20+, CD 22+, CD 11c+/-, CD 5-, CD 23-, CD 25-, HLA DR+, SmIg+. Differential diagnosis with other chronic lymphoproliferative disorders, particularly chronic lymphocytic leukemia, hairy cell leukemia, prolymphocytic leukemia, follicular and mantle-cell lymphoma in leukemic phase, is based on clinical and immunocytomorphologic criteria. Bone marrow biopsy shows involvement of different degree and pattern; splenic involvement mostly occurs in the white pulp; hepatic nodules in portal areas may be present. Cytogenetic alterations are often present but not specific, such as increased serum LDH and monoclonal gammopathy. No therapy should be made in asymptomatic patients. In case of systemic symptoms, symptomatic splenomegaly or cytopenias, treatment may consist on splenectomy, splenic irradiation or alkylating agents. A case of splenic lymphoma with circulating villous lymphocytes is reported; differential diagnosis, particularly with other B lymphoproliferative disorders, is discussed.

[Plasmocytoma of the testis. Description of a clinical case and review of the literature]. / Plasmocitoma del testicolo. Descrizione di un caso clinico e revisione della letteratura.

Extraskeletal involvement of the testis during multiple myeloma is a rare disease; primary extraosseus myeloma of the testis is even more unusual, and shows progression to typical multiple myeloma after orchiectomy in most cases. A case-report of a multiple myeloma with testicular involvement is discussed; radiotherapy was performed successfully, instead of surgery, but diffuse skeletal lesions showed progression in spite of chemotherapy. A short review of the literature on this subject is made.

[Stage classification of chronic lymphatic leukemia. A retrospective analysis of 263 cases]. / La classificazione in stadi della leucemia linfatica cronica. Analisi retrospettiva di 263 casi.

We have analyzed 263 consecutive patients with chronic-lymphocytic leukemia. They all have been studied according to five different staging systems respectively proposed by Rai (1975), Binet (1977), Binet again (1981), Baccarini (1982) and Rozman (1984). All these procedures proved to be effective, because they divided our cases in groups with significant differences in survival time. The paper displays features and usefulness of each staging system.

Electronic pupillometry for investigating pupil reactivity to different exteroceptive stimuli: applications and limits.

Iris neuromuscular junction represents a site of reciprocal interactions of sympathetic and parasympathetic innervation and can be considered a useful tool to investigate both systems in physiological and pathological conditions. In this study 35 healthy subjects of different ages were examined by an infrared TV pupillometer to assess darkness and light adaptation, as well as pupillary response to light and to exteroceptive stimulation (RIII reflex). A progressive impairment of pupil adaptability to light stimuli with aging was also observed, while a significant correlation was found between the intensity of electrical stimulation of the sural nerve and the percent increase in pupil diameter. The evaluation of pupil responsiveness is considered for its possible applications in various neurological disorders.

Primary cardiac lymphoma. A case report and review.

Primary cardiac lymphoma is classically defined as an extranodal non-Hodgkin's lymphoma exclusively located in the heart and/or pericardium. However, over the last few years, this definition has been extended to include other localizations on condition that these are clearly less important then a cardiac site, that must remain the first, during the illness course, and the most important for its entity. PCL is extremely rare in immunocompetent patients, accounting for 1.3% of all cardiac tumours and 0.5% of all extranodal lymphomas, but it has been encountered with increasing frequency in patients with AIDS or other severe immunodepressive syndromes. PCL is difficult to diagnose, especially during the early stage of the disease, because of its non-specific clinical manifestations, the limited possibility of using non-invasive diagnostic techniques, and difficulties or delays in applying invasive methods. The malignancy of its histotypes and its delicate location are responsible for its rapid and frequently unfavourable evolution. Successful treatment, which is mainly based on anthracycline-containing polychemotherapies, is heavily dependent on an early diagnosis. After a general review of the literature, the authors describe the clinical case of a patient with a PCL that had a secondary central nervous system location, treated with polychemotherapy and autologous peripheral blood stem cell transplantation. Emphasis is placed on the fact that it is more difficult to eradicate the disease from the central nervous system than from the heart.

[Colliculus hemorrhage]. / Hémorragies du colliculus.

We report the case of a patient with mesencephalic hematoma involving only the quadrigeminal plate. One case of superior and 3 cases of inferior colliculus hematoma have already been reported. Involvement of the quadrigeminal plate frequently follows a pontine or an anterior mesencephalic hemorrhage. The cause of these hematomas may be due to cryptic malformations of the quadrigeminal plate or primitive small size hemorrhages possibly related to the nature of the arterial system. Patients with inferior colliculus lesions present a typical symptomatology consisting of trochlear nerve palsy contralateral to the lesion or bilateral, contralateral hemiparesthesiae and acuphenes. Superior colliculus lesion causes upgaze palsy, visual blurring, dizziness and left upper lip paresthesiae. The cause of the different signs and symptoms in both types of lesion are discussed.

[Indications for x-rays of the skull and cervical spine: an open question]. / Indicazioni alle radiografie del cranio e della colonna cervicale: problematica aperta.

During the first six months of 1990, a study was carried out on a group of patients examined at the Neuroradiology Department of a Neurological Institute for skull and cervical spine X-rays. Kind of disturbances, the examination prescribed and patients' places of origin were taken into consideration. We studied 174 patients: 108 suffering from headache, 28 from cervical arthrosis, and the others from miscellaneous diseases. Male/Female ratio (M/F) was lower in the group affected by headache; the age was more advanced in the group affected by cervical arthrosis. Skull X-rays were usually normal in headache patients; cervical X-rays were not informative in cervical arthrosis patients. We can conclude that only through a different relationship between the prescribing physician and the Radiologist it will be possible to approach the justification and optimization criteria of medical radiological exposure.

[Lymphoma of the prostate: case reports and subject review]. / Il linfoma della prostata: contributo clinico e revisione dell'argomento.

Malignant lymphomas involving the prostate are rare whether as primary lymphoma or as secondary to generalized disease. Middle age, histotype prevalently non Hodgkin, intermediate and high grade of malignancy, symptoms of bladder outflow obstruction, diagnosis generally made after histological examination, severe prognosis are the most important features that result from literature review. The evaluation of therapeutic treatments is difficult as most reports do not include a sufficient number of cases. The Authors presenting two cases of lymphoma of the prostate point out the usefulness of radiotherapy since the prostate is usually a bulky seat of disease and suggest the combination with multiple drug chemotherapy for intermediate and high grade of malignancy and in advanced stages. The authors suggest that prognosis depends on histotype rather than on prostatic involvement of disease.